Comminution of concretions in vivo using extracorporeally generated shock waves (lithotripsy) is a recent medical practice, particularly in the treatment of urinary stone and biliary stone disease. Prior art describes various devices and methods for generating high-intensity, focused shock waves for the fragmentation of concretions inside a human being. U.S. Pat. No. 3,942,531 by Hoff, et al. discloses the use of a spark gap discharge in water to generate a shock wave within an ellipsoidal reflector which couples and focuses the shock wave to fragment kidney stones inside the body. Hahn, et al. in U.S. Pat. No. 4,655,220 disclose a device using a coil and a mating radiator, in the form of spherical segment, to produce magnetically induced self-converging shock waves. Wurster, et al. in U.S. Pat. Nos. 4,821,730 and 4,888,746, disclose the use of piezoelectric elements arranged in mosaic form on a spheroidal cap to produce focused high-intensity shock waves at the geometric center of the cap, where the concretion must be placed.
Despite the different principles used for shock wave generation, all these devices produce shock waves of a similar waveform, which can be characterized by a compressive phase consisting of a rapid shock front with a positive peak pressure up to 100 MPa, followed by a rarefaction (negative) phase with a negative peak pressure up to 10 MPa and with a few microseconds duration. It is also well known in the art that the negative phase of an incident shock wave can induce transient cavitation bubbles in the focal region.
It is further known in the art that when cavitation bubbles collapse near a stone surface, microjets will be produced due to the asymmetric collapse of the cavitation bubbles. These microjets impinge violently onto the stone surface and cause stone fragmentation. Experiments have shown that using the same shock wave generator at the same intensity level, a stone immersed in glycerol (a cavitation inhibitive medium) will not be damaged, while the same stone immersed in an aqueous solution such as water (a cavitation promotive medium) can be fragmented, despite the fact that the transmission of the shock wave energy in both cases is the same. It is established in the art that shock wave induced cavitation and the resultant microjet impingement is the primary mechanism for stone fragmentation. Furthermore, when shock wave-induced cavitation bubbles collapse near tissue surfaces, they can cause tissue injury through shock wave emission, the generation of high-temperatures, microjets, and the shear stresses associated with rapid bubble oscillation.
The present invention is based upon the discovery that the collapse of a cavitation bubble cluster can be controlled so as to cause increased concretion comminution by imposing an impinging shock wave of appropriate shape and intensity to collapse the bubble cluster from its outer layer into an inner layer collectively.
The collapse of a cavitation bubble by an impinging shock wave is found to be asymmetric, leading to the formation of a liquid jet which travels along the direction of the impinging shock wave. When occurring in water the liquid jet will be a water jet. It has been discovered that the collapse of a cavitation bubble can be controlled and guided by an incident shock wave, provided that this shock wave is applied at the correct time in the life of a cavitation bubble. It is further known in the art that the collapse of a cavitation bubble cluster by an impinging shock wave can concentrate 80% to 90% of the cavitation bubble energy from an outer layer to an inner layer, when these cavitation bubbles are forced to collapse in sequence by the incident shock wave. This concerted, controlled collapse of a cavitation bubble cluster by an impinging shock wave is found to produce an efficient concentration of the cavitation energy towards the center of the bubble cluster, where the concretion is located. Because the cavitation energy is directed towards and concentrated on the target concretion, tissue injury associated with the comminution of the concretion is reduced. Therefore, the comminution of concretions in vivo utilizing controlled, concentrated cavitation energy has the advantage of increased fragmentation efficiency with reduced tissue injury.
Riedlinger, in U.S. Pat. No. 5,209,221, discloses a device for generating sonic signals for limiting, preventing or regressing the growth of pathological tissue in vivo. The sonic signal, consisting of at least one rarefaction phase with a negative sonic pressure amplitude with a value greater than 2.times.10.sup.5 Pa, is radiated with a carrier frequency exceeding 20 kHz, a sonic pulse duration, T, of less than 100 microseconds and a pulse recurrence rate of less than 1/(5T). Thus, the time delay between two adjacent sonic pulses is greater than 500 microseconds. Since experiments have shown that the transient cavitation bubble clusters generated by all current lithotripsy devices last less than 400 microseconds, it is clear that by using the sonic pulse sequence as disclosed by Riedlinger, the ensuing sonic pulses will not be able to control the collapse of the cavitation bubble cluster induced by the initial sonic pulse.
Similarly, Cathignol, et al. in U.S. Pat No. 5,219,401 disclose an apparatus for the selective destruction of biological materials, including cells, soft tissues, and bones. The injection of gas bubble precursor microcapsules, having diameters preferably in the 0.5 to 300 microns range and made from materials such as lecithin, into the blood stream is used by Cathignol, et al. as the primary means of generating gas bubbles in vivo. Although the phenomenon of cavitation provoked by an ultrasonic wave generator working in a frequency range of 10.sup.4 to 10.sup.5 Hz is described, the sonic pulse sequence is not specified. As we have now discovered, the forced collapse of cavitation bubbles to produce fluid microjets for the enhanced comminution of concretions requires a specified relationship between the first, cavitation-inducing, acoustic pulse and the second, cavitation-collapsing, acoustic pulse. In addition, we have now also discovered that the second, cavitation-collapsing, acoustic pulse must have a compressive (positive) phase with a long duration and only a small, or no, tensile (negative) component.
Reichenberger, in U.S. Pat. No. 4,664,111, discloses a shock wave tube for generating time-staggered shock waves by means of a splitting device, such as a cone, for the fragmentation of concrements in vivo. Reichenberger discloses that the effects of the shock waves can be improved if they are so closely spaced in time that they overlap in their action on the concrement. The effects of shock wave induced cavitation are not considered or mentioned by Reichenberger.
None of the prior art teaches the use of a secondary shock wave, imposed at a specified time delay, to control the collapse of a transient cavitation bubble cluster induced by a primary shock wave. Without this time sequenced second shock wave, it has now been discovered that the efficiency of comminuting concretions in vivo by shock wave lithotripsy will be low, and the concomitant risk for tissue injury due to the uncontrolled cavitation energy deposition during the procedure will be correspondingly increased.
In the presently disclosed spark gap (electrohydraulic), electromagnetic, and piezoelectric shock wave generators, cavitation bubbles are formed after the passage of the incident shock wave. Furthermore, the shock wave-induced cavitation bubble clusters are transient, lasting for less than 400 microseconds, a time much shorter than the interval of shock wave delivery. Therefore, in presently used lithotripsy devices the collapse of the transient cavitation bubble cluster occurs in an uncontrolled, random fashion, resulting in only a small portion of the collapsing energy, typically less than 10%, being transmitted towards the stone surface. Much of the cavitation energy is either dissipated or consumed by surrounding tissue. Consequently, large numbers of shock waves are needed for adequate stone fragmentation, and as a consequence concomitant tissue injury is also produced by current shock wave generators. Using present lithotripsy devices, more than 4,000 pulses may be needed to produce desired stone comminution, while significant tissue damage may accompany this process.
The disclosed prior art uses uncontrolled, shock wave-induced cavitation for the fragmentation of concretions in vivo. Because cavitation bubble collapse is uncontrolled in devices disclosed by the prior art, the fragmentation efficiency is low, and thus the number of required acoustic pulses for producing adequate stone comminution is high. Furthermore, the method and apparatus of the prior art has a high risk for tissue injury due to the random deposition of the cavitation energy to adjacent tissue when the cavitation bubbles collapse.